24-hour Ambulatory Blood Pressure is Linked to Chromosome 18q21-22 and Genetic Variation of NEDD4L Associates with Cross-Sectional and Longitudinal Blood Pressure in Swedes.
(2006) In Kidney International 70(3). p.562-569- Abstract
- Numerous linkage studies have indicated chromosome 18q21–22 as a locus of importance for blood pressure regulation. This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC). In a linkage study of 16 markers (including two single nucleotide polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70–104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we subsequently showed that a NEDD4L gene variant... (More)
- Numerous linkage studies have indicated chromosome 18q21–22 as a locus of importance for blood pressure regulation. This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC). In a linkage study of 16 markers (including two single nucleotide polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70–104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we subsequently showed that a NEDD4L gene variant (rs4149601), which by alternative splicing leads to varying expression of a functionally crucial C2 domain, was associated with diastolic blood pressure (DBP) (P=0.03) and DBP progression over time (P=0.04). A genotype combination of the rs4149601 and an intronic NEDD4L marker (rs2288774) was associated with systolic blood pressure (SBP) (P=0.01), DBP (P=0.04), and progression of both SBP (P=0.03) and DBP (P=0.05) over time. A quantitative transmission disequilibrium test in the family material of the rs4149601 supported this NEDD4L variant as being at least partially causative of the linkage result. In conclusion, our findings suggest that the chromosome 18 linkage peak at 82.25 cM is explained by genetic NEDD4L variation affecting cross-sectional and longitudinal blood pressure, possibly as a consequence of altered NEDD4L interaction with ENaC. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1137069
- author
- Fava, Cristiano LU ; Wowern, Fredrik LU ; Berglund, Göran LU ; Carlson, Jonas LU ; Hedblad, Bo LU ; Nilsson, Lena LU ; Burri, Philippe LU ; Almgren, Peter LU and Melander, Olle LU
- organization
-
- Translational Muscle Research (research group)
- Cardiovascular Research - Hypertension (research group)
- Internal Medicine - Epidemiology (research group)
- Cardiology
- Cardiovascular Research - Epidemiology (research group)
- Diabetes - Islet Patophysiology (research group)
- Department of Clinical Sciences, Malmö
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- blood pressure, linkage, NEDD4L, genetics
- in
- Kidney International
- volume
- 70
- issue
- 3
- pages
- 562 - 569
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:33746480779
- wos:000239390200023
- pmid:16788695
- ISSN
- 1523-1755
- DOI
- 10.1038/sj.ki.5001590
- language
- English
- LU publication?
- yes
- id
- e3746f4b-30f6-486d-8bee-7a4f6f9dbe35 (old id 1137069)
- date added to LUP
- 2016-04-01 16:10:20
- date last changed
- 2024-05-09 23:10:27
@article{e3746f4b-30f6-486d-8bee-7a4f6f9dbe35, abstract = {{Numerous linkage studies have indicated chromosome 18q21–22 as a locus of importance for blood pressure regulation. This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC). In a linkage study of 16 markers (including two single nucleotide polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70–104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we subsequently showed that a NEDD4L gene variant (rs4149601), which by alternative splicing leads to varying expression of a functionally crucial C2 domain, was associated with diastolic blood pressure (DBP) (P=0.03) and DBP progression over time (P=0.04). A genotype combination of the rs4149601 and an intronic NEDD4L marker (rs2288774) was associated with systolic blood pressure (SBP) (P=0.01), DBP (P=0.04), and progression of both SBP (P=0.03) and DBP (P=0.05) over time. A quantitative transmission disequilibrium test in the family material of the rs4149601 supported this NEDD4L variant as being at least partially causative of the linkage result. In conclusion, our findings suggest that the chromosome 18 linkage peak at 82.25 cM is explained by genetic NEDD4L variation affecting cross-sectional and longitudinal blood pressure, possibly as a consequence of altered NEDD4L interaction with ENaC.}}, author = {{Fava, Cristiano and Wowern, Fredrik and Berglund, Göran and Carlson, Jonas and Hedblad, Bo and Nilsson, Lena and Burri, Philippe and Almgren, Peter and Melander, Olle}}, issn = {{1523-1755}}, keywords = {{blood pressure; linkage; NEDD4L; genetics}}, language = {{eng}}, number = {{3}}, pages = {{562--569}}, publisher = {{Nature Publishing Group}}, series = {{Kidney International}}, title = {{24-hour Ambulatory Blood Pressure is Linked to Chromosome 18q21-22 and Genetic Variation of NEDD4L Associates with Cross-Sectional and Longitudinal Blood Pressure in Swedes.}}, url = {{http://dx.doi.org/10.1038/sj.ki.5001590}}, doi = {{10.1038/sj.ki.5001590}}, volume = {{70}}, year = {{2006}}, }